Azacitidine in Combination With Low Dose Intensity Venetoclax in Patients With AML Incl. Explorative AML Profiling

Multi-center phase II study of standard azacytidine treatment (AZA; D1-D7, 75mg/m2 qd) in combination with a short duration of "low-dose" venetoclax treatment (LD-VEN; D1-D14 before CR and D1-D7 after CR, 400mg qd) per 28 days cycle for elderly/unfit (arm 1) and relapsed/refractory (arm 2) patients with acute myeloid leukemia. AML patients will be subjected to conventional diagnostic workup to assess if they fulfil eligibility criteria. As part of the exploratory trial program, bone marrow (BM) and peripheral blood (PB) samples will be subjected to functional AML profiling including OMICs analyses and immediate ex vivo drug sensitivity and resistance testing (DSRT). The treatment period with AZA/LD-VEN begins after completion of the diagnostic workup period, and includes drug treatment, clinical assessment, QoL assessment, and analysis of relevant follow-up BM and PB samples according to a detailed study event schedule. Patients will receive repeated cycles of treatment with AZA (D1-D7, 75mg/m2 qd) in combination with LD-VEN (D1-D14 before CR and D1-D7 after CR, 400mg qd) every 4 weeks. Patients exhibiting clinical response will continue treatment with AZA/LD-VEN for a maximum of two years or until withdrawal of consent, disease progression, unacceptable toxicity, intolerance, lack of compliance, unresponsiveness after three cycles of study treatment, or if they obtain CR and proceed to allogeneic stem cell transplantation. Clinical response (CR/CRi/MLFS=morphologic leukemia-free state/PR=partial remission), survival information (OS/DOR=duration of response/EFS=event-free survival), and QoL data will be collected for all patients independently on their response to AZA/LD-VEN treatment. Survival information and post-treatment follow-up (i.e. all post-treatment AML therapies including dates of initiation and completion, the date and cause of death) will be collected every three months for the first two years and thereafter annually for the following three years after End-Of-Treatment or withdrawal from study treatment, or until death of the patient. The exploratory program will validate the feasibility of comprehensive OMICs profiling and ex vivo drug sensitivity and resistance testing in a clinical setting to predict responders and non-responders to AZA/LD-VEN therapy. The exploratory AML profiling program is expected to identify biomarkers as well as novel drugs and drug combinations applicable for treatment of AML patients that are refractory or suffer from relapse after AZA/LD-VEN treatment in future clinical trial initiatives.